Transcriptomics

Dataset Information

3

5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer [Methylation27 Array]


ABSTRACT: The discovery of cytosine hydroxymethylation (5-hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behavior in colon cancer. 5-hmC is globally reduced in proliferating cells such as colon tumors and the gut crypt progenitors, from which tumors can arise. Here, we show that colorectal tumors and cancer cells express Ten-Eleven Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5-hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5-hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Together our results indicate that promoters that acquire 5-hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5-hmC in tumors. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation. DNA methylation levels were measured in genomic DNA extracted from primary colon tissues.

ORGANISM(S): Homo sapiens  

SUBMITTER: Rory Stark   Mark Dunning  Thomas Carroll  Sarah Vowler  Silvia Halim  Santiago Lewis 

PROVIDER: E-GEOD-47071 | ArrayExpress | 2015-02-03

SECONDARY ACCESSION(S): GSE47071PRJNA206431

REPOSITORIES: GEO, ArrayExpress

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